Phase II study of izalontamab (SI-B001) in combination with paclitaxel or docetaxel in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Abstract

6019 Background: Izalontamab is a bispecific antibody targeting EGFR and HER3. Here we present safety and efficacy results from a phase II study on izalontamab in combination with paclitaxel/docetaxel in patients with R/M HNSCC. Methods: Patients with R/M HNSCC who had progressed on prior anti-PD-(L)1 therapy, with or without platinum-based chemotherapy, and received no more than two prior lines of treatment were enrolled. Izalontamab was administered at 12mg/kg QW in combination with paclitaxel (80mg/m 2 IV QW) (for patients without prior exposure to paclitaxel) or docetaxel (35mg/m 2 IV D1D8D15 Q4W) (for patients with prior exposure to paclitaxel). Primary endpoint was investigator-assessed ORR. Secondary endpoints included PFS, OS, DCR, and DoR. Results: As of Nov 7, 2025, a total of 45 patients (44 HNSCC and 1 sinnonasal) were enrolled, of whom 35 (77.8%) received one prior line of therapy and 10 (22.2%) received two prior lines of therapy. HNSCC patients who received at least one dose of study drug were included in the analysis. Median follow-up was 15.0 months. Overall, ORR was 43.2%, confirmed ORR was 31.8%, median PFS was 4.0 months, and median OS was 10.0 months. In patients treated with izalontamab combo with paclitaxel (n = 34), ORR was 52.9%, confirmed ORR was 41.2%, median PFS was 5.4 months, and median OS was 11.2 months. Grade≥3 TRAEs occurred in 57.8% of patients. The most common grade≥3 TRAE was leukopenia (20.0%), followed by neutropenia (15.6%), rash (13.3%), and anemia (8.9%). One (2.1%) patient discontinued study treatment due to TRAE. No treatment-related death was observed. Conclusions: Izalontamab in combination with paclitaxel showed encouraging antitumor activity and a manageable safety profile in patients with R/M HNSCC who were previously treated with anti-PD-(L)1 therapy. Clinical trial information: NCT05054439 . Izalontamab+Paclitaxel(N=34) Izalontamab+ Docetaxel(N=10) Total(N=44) ORR, % (95% CI) 52.9 (35.1, 70.2) 10.0 (0.3, 44.5) 43.2 (28.3, 59.0) cORR, % (95% CI) 41.2 (24.6, 59.3) 0 31.8 (18.6, 47.6) DCR, % (95% CI) 73.5 (55.6, 87.1) 30.0 (6.7, 65.2) 63.6 (47.8, 77.6) Median DOR (mo) (95% CI) 5.0 (3.7, 11.0) NR (NR, NR) 5.0 (3.7, 11.0) Median PFS (mo) (95% CI) 5.4 (3.9, 6.6) 1.5 (0.4, 3.6) 4.0 (2.8, 5.5) Median OS (mo) (95% CI) 11.2 (6.6, 19.3) 6.6 (0.4, 13.8) 10.0 (6.6, 13.8)